We request the Illumina Solexa GAIIx system, which will be an essential "next generation" sequencing platform for a wide range of NIH funded projects at the greater Chicago metropolitan area. This new machine will be housed at the High-Throughput Genomic Analysis Core (HGAC) of the Joint Institute of Genomics and Systems Biology (IGSB) at the University of Chicago and Argonne National Laboratory (ANL) http://www.igsb.org/services/index.php?p=hgac. Importantly, the addition of this capacity will enable NIH funded investigators at universities such as Loyola University and University of Illinois at Chicago to gain access to state-of-the-art technology. Investigators at The University of Chicago and Northwestern University already make use of existing facility, but our capacity is limited due to major NIH funded grants such as an NHGRI modENCODE project (U01HG004264) already occupying existing machines at 100% capacity (two Solexa GAII machines and one Roche GS-FLX 454 sequencer). Specifically, multiple NIH funded investigators from the University of Chicago Cancer Center and who are part of the IGSB-led "1000 Chicago Cancer Transcriptomes Initiative" will be enabled by the requested instrument. Also, investigators in the Chicago Center for Systems Biology (CCSB), one of ten National Centers for Systems Biology funded by NIGMS, would be supported with this instrument. Funding this instrument request would thus leverage not only the existing HGAC infrastructure, but also multiple NIH research funded projects of dozens of investigators in the Chicago area who require whole-genome sequencing and re-sequencing, transcriptome sequencing, de novo sequencing, SNP discovery, gene expression, small RNA discovery, or ChIP-seq. Critically important for success and immediate impact, the machine would be integrated with an existing production service pipeline that includes trained technical staff with experience in all aspects of nucleic acid isolation, library construction, cluster generation and quality control for Solexa;as well as a LIMS, computing, primary analysis and data distribution infrastructure that has been developed with a team of bioinformatics experts in IGSB (www.igsb.org) over the last 18 months. This will allow the machine to have immediate impact on NIH investigators at four universities in Chicago.